阿利西尤单抗（一种全人源PCSK9单克隆抗体）在接受最大耐受剂量他汀类药物治疗但高胆固醇血症控制不佳的高心血管风险患者中的疗效和安全性：ODYSSEY COMBO I和II试验的原理与设计
Efficacy and safety of alirocumab, a fully human PCSK9 monoclonal antibody, in high cardiovascular risk patients with poorly controlled hypercholesterolemia on maximally tolerated doses of statins: rationale and design of the ODYSSEY COMBO I and II trials.
作者信息
Colhoun Helen M, Robinson Jennifer G, Farnier Michel, Cariou Bertrand, Blom Dirk, Kereiakes Dean J, Lorenzato Christelle, Pordy Robert, Chaudhari Umesh
机构信息
University of Dundee, Dundee, Scotland DD2 4BF, UK.
出版信息
BMC Cardiovasc Disord. 2014 Sep 20;14:121. doi: 10.1186/1471-2261-14-121.
BACKGROUND
Alirocumab is a fully human monoclonal antibody to proprotein convertase subtilisin kexin type 9 (PCSK9) under investigation for treatment of hypercholesterolemia and reduction of cardiovascular events.
METHODS/DESIGN: The COMBO studies, part of the Phase 3 ODYSSEY clinical trial program, are designed to evaluate the efficacy and safety of alirocumab as add-on therapy to stable, maximally tolerated daily statin, with or without other lipid-lowering therapy (LLT), in a planned 966 patients with hypercholesterolemia at high cardiovascular risk. COMBO I ( http://clinicaltrials.gov/show/NCT01644175) is placebo-controlled, with a double-blind treatment period of 52 weeks, and 306 planned patients who may receive other LLTs in addition to statin therapy. COMBO II ( http://clinicaltrials.gov/show/NCT01644188) has a double-blind treatment period of 104 weeks, comparing alirocumab with ezetimibe in 660 planned patients receiving statin therapy (but no other LLTs). The primary efficacy endpoint is the difference between treatment arms in percent change in low-density lipoprotein cholesterol (LDL-C) from baseline to week 24. Both studies utilized a starting dose of alirocumab 75 mg every 2 weeks (Q2W; administered as 1 mL solution via auto-injector). Patients with LDL-C levels ≥70 mg/dL after 8 weeks of treatment were up-titrated in a blinded manner at week 12 to alirocumab 150 mg Q2W (also 1 mL auto-injector).
DISCUSSION
In conclusion, the COMBO studies will provide information on the long-term efficacy and safety of alirocumab in high-risk patients when administered in addition to maximally tolerated statin therapy, with a flexible dosing strategy which allows for individualized therapy based on the degree of LDL-C lowering needed to achieve the desired treatment response.
TRIAL REGISTRATIONS COMBO I
NCT01644175 ( NCT01644175).
COMBO II
NCT01644188 ( NCT01644188).
背景
阿利西尤单抗是一种全人源单克隆抗体，靶向前蛋白转化酶枯草溶菌素9型（PCSK9），目前正处于研究阶段，用于治疗高胆固醇血症和降低心血管事件风险。
方法/设计：COMBO研究是3期ODYSSEY临床试验项目的一部分，旨在评估阿利西尤单抗作为稳定的、最大耐受剂量的每日他汀类药物的附加疗法（联合或不联合其他降脂治疗[LLT]），对计划入组的966例具有高心血管风险的高胆固醇血症患者的疗效和安全性。COMBO I（http://clinicaltrials.gov/show/NCT01644175）为安慰剂对照试验，双盲治疗期为52周，计划入组306例患者，这些患者除他汀类治疗外可能接受其他LLT。COMBO II（http://clinicaltrials.gov/show/NCT01644188）的双盲治疗期为104周，在660例接受他汀类治疗（但未接受其他LLT）的计划入组患者中，将阿利西尤单抗与依折麦布进行比较。主要疗效终点是治疗组之间从基线到第24周低密度脂蛋白胆固醇（LDL-C）百分比变化的差异。两项研究均采用阿利西尤单抗起始剂量为每2周75mg（Q2W；通过自动注射器以1mL溶液给药）。治疗8周后LDL-C水平≥70mg/dL的患者在第12周以盲法上调至阿利西尤单抗150mg Q2W（也是1mL自动注射器）。
讨论
总之，COMBO研究将提供有关阿利西尤单抗在高风险患者中，除最大耐受剂量他汀类治疗外给药时的长期疗效和安全性信息，其灵活的给药策略允许根据实现所需治疗反应所需的LDL-C降低程度进行个体化治疗。
试验注册 COMBO I：NCT01644175（NCT01644175）。
COMBO II
NCT01644188（NCT01644188）。
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